JP2021536271A - Injection device - Google Patents

Abstract

The present disclosure is an injection device: with a housing; with a carrier disposed within the housing to hold a syringe with a needle at one end; in an extended position and a retracted position with respect to the housing. Includes an axially movable needle sleeve between; an urging element configured to urge the needle sleeve towards an extension position; the injection device extends the needle sleeve after use of the injection device. The locking mechanism includes a locking mechanism configured to lock in position; a first locking member provided to the carrier and protruding from the carrier; provided to the needle sleeve and movable between the relaxed position and the deflection position. Includes a second locking member, including a deflectable arm; where the housing engages with the second locking member to deflect the second locking member as the needle sleeve is moved to the retracted position. Includes an inwardly projecting boss that moves to position; when the second locking member is in the deflection position, the first locking member does not engage the second locking member; the second locking member is in the relaxed position. With respect to the injection device, the second locking member blocks the first locking member when the needle sleeve is in the extended position, thereby hindering the movement of the needle sleeve back to the retracted position. [Selection diagram] FIG. 6

Description

The present invention relates to an injection device, a method of activating the injection device, and a method of assembling the injection device.

Injection devices such as automatic syringes are known in the art for administering a drug to a patient's injection site. Such injection devices often include a body and a cap, the needle syringe is located on the body, and the cap is detachably attached to the body to shield the needle of the needle syringe. To administer the drug, the cap is first removed from the body and the needle is exposed. A needle is then inserted into the patient's body at the injection site to administer the drug.

It is important to prevent access to the needle after the injection has been made. A movable needle sleeve and locking means can be provided to ensure that the needle is covered and access to the needle is restricted after the drug has been administered; this is because sharp needles cause injury. It can also act as an indicator that the injection device has already been used.

An object of the present invention is to provide an improved injection device.

According to the first embodiment, the injection device is: a housing; a carrier disposed within the housing to hold a syringe having a needle at one end; and located within the housing and extends with respect to the housing. Includes a needle sleeve that is axially movable between the position and the retracted position; and an urging element that is configured to urge the needle sleeve towards the extension position; the injection device is after use of the injection device. The locking mechanism includes a locking mechanism configured to lock the needle sleeve to the extended position; with a first locking member provided to the carrier and protruding from the carrier; provided to the needle sleeve, relaxed and deflected positions. Includes a second locking member, including a deflectable arm that is movable between and; where the housing engages the second locking member as the needle sleeve is moved to the retracted position. Includes an inwardly projecting boss that moves the locking member to the deflection position; when the second locking member is in the deflection position, the first locking member does not engage the second locking member; There is an injection device in which when is in the relaxed position and the needle sleeve is in the extended position, the second locking member blocks the first locking member, thereby hindering the movement of the needle sleeve back to the retracted position.

Preventing the needle sleeve from moving back to the retracted position may improve the safety of the device, as access to the needle can be restricted after the injection has been made. It may also act as an indicator that the injection device has been used and can further avoid accidental injury. The mechanisms described above can be particularly beneficial when a syringe with a short needle is needed.

As used herein, "short" may refer to a needle length of less than about 12.5 mm, typically about 6 mm, but the injection devices described herein are. It can be understood that it can also be used for needle lengths of 12.5 mm and above. The length of the needle can be the length from the distal end of the syringe glass to the tip of the needle.

As used herein, the terms distal and proximal refer to the orientation with respect to the injection device. The term "distal" refers to a location relatively close to the injection site, and the term "proximal" refers to a location relatively far from the injection site.

There are several advantages to using a short needle for the injection device; the overall size of the device is smaller compared to a device with a longer needle, the injection time can be improved, and a more viscous fluid. Injections can be made, the storage load and the impact force of the stopper can be reduced, and finer gauge needles can be used without compromising on injection time. Finer gauge needles can also mean less pain for the user and can be particularly beneficial in pediatric applications.

In one embodiment, the needle sleeve may extend further out of the housing in an extended position rather than a retracted position. In a further embodiment, the needle sleeve may be movable between three positions: start position, retracted position, and extended position, and the needle sleeve extends further out of the housing at an extended position than the start position and from the retracted position. May extend further out of the housing at the starting position.

In one embodiment, the needle sleeve is retractable between the housing and the carrier.

In one embodiment, the deflectable arm may have a first end fixedly attached to the rest of the needle shield and a second free end away from the first end.

The mobility of the injection device between the three positions may help to perform priming of the locking mechanism during device assembly by machine rather than manually. However, the user can understand that the locking mechanism can be primed before activating the injection device. For the elderly or frail, or in a hurry, or those who require easier operation of the device, it is desirable to simplify the operation of the injection device by priming the locking mechanism during the assembly phase.

In one embodiment, the first and second locking members are configured such that the first locking member does not engage the second locking member when the second locking member is in a deflection position.

In one embodiment, the first and second locking members are such that the second locking member blocks the first locking member when the second locking member is in the relaxed position and the needle sleeve is in the extended position. It is composed of.

In one embodiment, the first locking member comprises a protrusion.

In one embodiment, when the needle sleeve is in the starting position, the deflectable arm may be in the relaxed position and the first locking member may be disposed distal to the free end of the deflectable arm. ..

The above or each arm can be deflectable in the circumferential direction. However, it will be appreciated by those skilled in the art that in other embodiments, the above or each arm may be deflectable in alternative directions, eg, radially or tangentially.

In one embodiment, the first and second locking members are axially aligned when the second locking member is in the relaxed position, but axially positioned when the second locking member is in the deflection position. It is out of alignment. This can allow the first locking member to move beyond the second locking member when the second locking member is in the deflection position, which allows the second locking member to move beyond the starting position. Provides means for engaging the first locking member, but can also block the second locking member when the second locking member is in the relaxed position.

In one embodiment, the deflectable arm can be laterally deflectable with respect to the axial direction of the injection device when the second locking portion is engaged by an inwardly projecting boss of the housing. .. Lateral deflection of the deflectable arm not only aids in easy assembly by aligning specific components, but also allows the second locking member to first lock when the second locking member is in the relaxed position. It can also be made possible to engage with the member.

The second locking member may be a pair of deflectable arms or a single deflectable arm urged against the surface of the needle sleeve or alternative component. It can be appreciated that the second locking member may be a pair of pivotable arms, which are rigid and can include a series of joints. There may be only one pivotable arm urged against a fixed surface of the injection device, such as the surface of the needle sleeve. It can be understood that the second locking member may be directed proximally; however, the second locking member may be directed distally. The deflectable arm may be substantially linear, and the free end of the deflectable arm may extend distally.

It can be beneficial for the second locking member to be a pair of deflectable arms; the equal force of each deflectable arm at the relaxed position with respect to the first locking member makes it easier for the first locking member. Can be retained or blocked.

In one embodiment, the above or each arm can be deflectable in the circumferential direction with respect to the housing. However, it will be appreciated by those skilled in the art that in other embodiments, the above or each arm may be deflectable in alternative directions, eg, radially or tangentially to the housing.

In one embodiment, the injection device may further include a removable cap. One advantage of the cap is that it can shield the needle when not in use, helping to ensure that the needle remains sterile prior to use. The cap may also reduce the risk of accidental activation of the injection device, for example when the device is dropped. When the cap is on the device, the interlocking portion of the cap can engage the corresponding interlocking portion of the needle sleeve, preventing accidental pushing down of the needle sleeve before the cap is removed.

In one embodiment, the first locking member may include a T-shaped boss protruding from the carrier. The first locking member may have a relatively narrow portion and a relatively wide portion, and the first locking member may be at least substantially rigid. The boss may project inward or outward of the carrier, with the inside facing the central axis of the injection device.

The T-shaped boss can be advantageous in the performance of the locking mechanism. The T-shaped head is easily held or blocked by the second locking member, but can still move over the second locking member when the second locking member is in the deflection position. The T-shaped boss can also be easily manufactured as part of the carrier.

In one embodiment, the inwardly projecting boss of the housing can be tapered toward the distal direction or shaped like an arrowhead. However, it can be understood that any shape that can force the second locking member of the needle sleeve to the deflection position can be appropriate.

Due to the tapering or arrow-like shape of the inwardly projecting boss, the inwardly projecting boss gradually pushes the second locking member into the deflection position and gradually releases the second locking member to the relaxed position. It will be possible to do. This gradual movement between positions can reduce the force on the second locking member and reduce the possibility of breakage or elastic deformation.

In one embodiment, the first locking member can include at least one rigid portion and the second locking member can include at least one flexible portion. The combination of the rigid and flexible portions can also reduce the force on the locking mechanism and reduce the possibility of damage or elastic deformation to the locking mechanism.

In one embodiment, the injection device can further include a syringe having a needle at one end. The syringe can contain the drug.

In one embodiment, the injection device may be an automatic syringe.

In one embodiment, it is a method of assembling an injection device: inserting a syringe with a needle into a carrier; moving the needle sleeve proximal to the housing to a first assembly position. In the first assembly position, the inwardly projecting boss of the housing engages the second locking member of the needle sleeve, moving the second locking member from the relaxed position to the deflection position.
A step of moving the carrier distally into the housing to a second assembly position, where the second locking member is in a deflection position and the first locking member is of a deflectable arm at the second assembly position. Disposed distal to the free end, the first locking member does not engage the second locking member, with the process;
In the process of releasing the needle sleeve, the urging element pushes the needle sleeve distally, the inwardly projecting boss disengages from the second locking member, and the second locking member is in the relaxed position. Movement, thereby placing the needle sleeve in the starting position, where the first locking member is located distal to the free end of the deflectable arm and the second locking member is in the relaxed position. There are ways that can be included.

Allowing mechanical priming of the locking mechanism during device assembly, rather than manually, is beneficial for the elderly or frail, or in a hurry, or those who require easier operation of the device. Can be. The starting position of the needle sleeve simplifies the operation of the injection device for the user.

In this method, the carrier is inserted into the subassembly containing the housing and the needle sleeve to the intermediate position before moving the needle sleeve to the housing to the first assembly position, followed by the needle sleeve in the first assembly position. After being moved to the assembly position, the carrier can be further moved distally within the housing to the second assembly position.

In one embodiment, the second locking member may have two deflectable arms; each deflectable arm is free with a first end fixedly attached to the rest of the needle sleeve. It may have a second end that is an end. In the second assembly position, the first locking member may be disposed between the two arms.

These and other aspects of the invention will be apparent from the embodiments described below and will be described in detail with reference to those embodiments.

Here, an embodiment of the present invention will be described merely as an example with reference to the accompanying drawings.

It is a schematic side view of an automatic syringe. FIG. 1A is a schematic side view of the automatic syringe of FIG. 1A, showing some internal components. FIG. 3 is a side view of an injection device with a locking mechanism, with corners cut out to illustrate some of the internal components. It is a perspective view of the carrier of FIG. It is a perspective view of a part of the needle sleeve of FIG. 2 which shows the 2nd locking member in a relaxed position. It is an enlarged view of the locking mechanism when the needle sleeve is in the start position. It is an enlarged view of the locking mechanism when the needle sleeve is in the retracted position. It is an enlarged view of the locking mechanism when the needle sleeve is in the extended position. FIG. 2 is a diagram of different stages of the locking mechanism in use of the device of FIG. It is a perspective view of the needle sleeve of the device of FIG. It is a perspective view of the housing of the device of FIG. FIG. 2 is a side view of the end of the needle sleeve, plunger, and housing of FIG. It is a side view of the component of FIG. 11 assembled at the start position. FIG. 2 is an enlarged schematic side view of the cap and needle sleeve of the device of FIG.

The drug delivery device described herein is configured to inject a drug into a patient. For example, delivery can be subcutaneous, intramuscular, or intravenous. Such devices can be operated by a patient or caregiver such as a nurse or doctor and can include various types of safety syringes, pen-type syringes, or automatic syringes. The device can include a cartridge-based system that requires perforation into the sealed ampoule prior to use. The volume of drug delivered by these various devices can range from about 0.5 ml to about 2 ml. Yet another device can include a high volume device (“LVD”) or patch pump, which adheres to the patient's skin over a period of time (eg, about 5, 15, 30, 60, or 120 minutes). It is configured to deliver a "large" volume of drug (typically about 2 ml to about 10 ml).

Also, in combination with a particular agent, the devices described herein may be customized to operate within the required specifications. For example, the device is customized to inject the drug within a specific time period (eg, about 3 to about 20 seconds for an automatic syringe, and about 10 to about 60 minutes for an LVD). Other specifications may include low or minimal levels of discomfort, or specific conditions related to human factors, shelf life, expiration date, biocompatibility, environmental friendliness, and the like. Such variability can be caused by a variety of factors, such as drugs with viscosities ranging from about 3 cP to about 50 cP. Therefore, drug delivery devices often include hollow needles ranging in size from about 25 to about 31 gauge. Typical sizes are 27 and 29 gauge.

The delivery device described herein may also include one or more automated functions. For example, one or more of needle insertion, drug injection, and needle retraction can be automated. Energy for one or more automation steps can be provided by one or more energy sources. The energy source can include, for example, mechanical, pneumatic, chemical, or electrical energy. For example, mechanical energy sources may include springs, levers, elastomers, or other mechanical mechanisms for storing or releasing energy. One or more energy sources can be combined into a single device. The device may further include gears, valves, or other mechanisms for converting energy into the movement of one or more components of the device.

Each automatic function of one or more of the automatic syringes is activated by an activation mechanism. Such activation mechanisms may include one or more of buttons, levers, needle sleeves, or other activation components. Invoking the automatic function can be a one-step or multi-step process. That is, the user may need to activate one or more activation components in order to trigger the automatic function. For example, in a one-step process, a user may press a needle sleeve against his body to trigger an injection of a drug. Other devices may require multi-step activation of automatic functions. For example, the user needs to push down the button and retract the needle sleeve to trigger the injection.

Further, the activation of one automatic function may activate one or more subsequent automatic functions, thereby forming an activation sequence. For example, activation of the first automatic function may activate at least two of needle insertion, drug injection, and needle retraction. Also, some devices may require a specific process sequence to give rise to one or more automated functions. Other devices may operate in a series of independent processes.

Some delivery devices can include one or more functions of safety syringes, pen-type syringes, or automatic syringes. For example, a delivery device may have a mechanical energy source configured to automatically inject a drug (as is normally found in an automatic syringe) and a dose setting mechanism (as is normally found in a pen-type syringe). Can include.

According to some embodiments of the present disclosure, exemplary drug delivery devices 10 are shown in FIGS. 1A and 1B. The device 10 is configured to inject the drug into the patient's body, as described above. The device 10 includes a housing 11, which is typically required to facilitate one or more steps of the delivery process with a reservoir (eg, a syringe) containing the drug to be injected. Includes components. The device 10 can also include a cap assembly 12 that can be detachably attached to the housing 11. Typically, the user cannot operate the device 10 without removing the cap 12 from the housing 11.

As shown, the housing 11 is substantially cylindrical and has a substantially constant diameter along the longitudinal axis AA. Housing 11 has a distal region D and a proximal region P.

The term "distal" refers to a location relatively close to the injection site, and the term "proximal" refers to a location relatively far from the injection site.

The device 10 also includes a needle sleeve 19 connected to the housing 11 and can allow the needle sleeve 19 to move relative to the housing 11. For example, the needle sleeve 19 can move in the longitudinal direction parallel to the longitudinal axis AA. Specifically, the movement of the needle sleeve 19 in the proximal direction can allow the needle 17 to extend from the distal region D of the housing 11.

The insertion of the needle 17 can be performed by several mechanisms. For example, the needle 17 is fixedly located relative to the housing 11 and initially located within the extended needle sleeve 19. Proximal movement of the needle sleeve 19 by disposing the distal end of the needle sleeve 19 with respect to the patient's body and moving the housing 11 distally exposes the distal end of the needle 17. Such relative movement allows the distal end of the needle 17 to extend into the patient's body. Such an insertion is called a "manual" insertion because the needle 17 is manually inserted by the patient manually moving the housing 11 into the needle sleeve 19.

Another form of insertion is "automatic", in which the needle 17 moves with respect to the housing 11. Such insertion can be triggered by the movement of the needle sleeve 19 or by another activation mode, such as the button 13. As shown in FIGS. 1A and 1B, the button 13 is located at the proximal end of the housing 11. However, in other embodiments, the button 13 may be located on the side surface of the housing 11.

Other manual or automatic functions can include lethal injection and / or needle retraction. Injection is the process by which a plug or piston 14 is moved from a proximal position inside the syringe 18 to a more distal position inside the syringe 18 to push the drug out of the syringe 18 through the needle 17. In some embodiments, the drive spring (not shown) is compressed before the device 10 is activated. The proximal end of the drive spring can be secured within the proximal region P of the housing 11, and the distal end of the drive spring can be configured to exert a compressive force on the proximal surface of the piston 14. After activation, at least a portion of the energy stored in the drive spring can be applied to the proximal surface of the piston 14. This compressive force acts on the piston 14 to move the piston 14 in the distal direction. Such distal movement acts to compress the liquid drug inside the syringe 18, pushing the liquid drug out of the needle 17.

After injection, the needle 17 can be retracted into the needle sleeve 19 or the housing 11. Retraction may occur when the needle sleeve 19 moves distally as the user removes the device 10 from the patient's body. This may occur when the needle 17 remains fixedly positioned with respect to the housing 11.

When the distal end of the needle sleeve 19 moves past the distal end of the needle 17 and the needle 17 is covered, the needle sleeve 19 can be locked.

Since the locking of the needle sleeve is based on the relative movement of the housing or needle and the needle sleeve, it is necessary to consider the length of the needle when considering a suitable locking mechanism. There are several advantages to using a short needle for the injection device; the overall size of the device is smaller compared to a device with a longer needle, the injection time can be improved, and a more viscous fluid. Injections can be made, the storage load and the impact force of the stopper can be reduced, and finer gauge needles can be used without compromising on injection time. Finer gauge needles can also mean less pain for the user and can be particularly beneficial in pediatric applications.

As used herein, "short" refers to a length of less than about 12.5 mm, typically about 6 mm as an example, but the devices described below are for needles of 12.5 mm or more. You can understand that it can also be used in terms of length. The length of the needle 17 can be the length from the distal end of the syringe 18 glass to the tip of the needle 17.

Next, referring to FIGS. 2 to 10, the injection device 20 according to the first embodiment of the present invention is shown. The injection device 20 is in the form of an automatic syringe 20 having the same configuration as the automatic syringe 10 described above in connection with FIGS. 1A and 1B, with the same configuration being given the same reference number. The device 20 has a carrier 21 including a receiving end 22 for receiving a syringe and a needle end 23, and the needle 17 of the syringe projects through the needle end 23 when received by the carrier 21. The receiving end 22 is larger than the needle end 23, the needle end 23 further includes a notch portion 24, and the carrier section 25 tapers towards the distal end of the carrier. The carrier 21 further includes a first locking member 26 consisting of at least one substantially rigid boss or protrusion 27. The carrier boss 27 has a body portion 28 and a head portion 29, but only the head portion is required, the head portion 29 is substantially T-shaped, and the body portion 28 is substantially linear. I can understand. However, one of ordinary skill in the art can understand that the head portion 29 may have any alternative shape, for example, but not limited to, arrowhead, V-shaped, arc or hook shape. The main body portion 28 may be non-linear.

For assembly of the injection device 20, the carrier 21 is inserted into a subassembly that includes a needle sleeve 19 and a housing 11. It can be understood that the carrier, needle sleeve, and housing are all assembled as part of the same stage. The needle sleeve 19 includes a needle sleeve leg 39 and a cutout portion 40. The needle sleeve 19 further includes a second locking member 30 including a pair of deflectable arms 31 attached to each other by struts 32. The struts are then connected to the rest of the needle sleeve 19 by three supports 33. It is also understood that the deflectable arm 31, strut 32, and support 33 can all be formed integrally with the needle sleeve 19, but they may be any combination of separate parts connected to each other. Can be done. The deflectable arm may be directly linked to the needle sleeve 19 and additional struts 32 or supports 33 may not be required. The support 33 may be more or less than three, or the struts 32 may be more or less than one, depending on the structural properties required by the second locking member 30. The needle sleeve 19 can have a pair of second locking members 30 disposed on both sides of the needle sleeve 19.

The deflectable arm 31 has a first end 36 fixedly attached to the rest of the needle sleeve 19 and a second opposite end 37 extending proximally from the first end. Have. The second end 37 is free and is not attached to the rest of the needle shield except through the first end 36. The deflectable arm also has an intermediate portion 38, which may be linear, bent inward towards each other, or include additional joints.

The housing 11 further includes an inwardly projecting boss 34 located towards the distal end of the housing 11. The inwardly projecting boss 34 may taper towards the distal end of the injection device 20. It can be understood that the inwardly projecting boss 34 may be integrally formed with the housing 11, but the inwardly projecting boss 34 may be a separate component connected to the housing 11. .. The inwardly projecting boss 34 engages with the second locking member 30 to force the deflectable arm 31 to move apart, opening a space between the two deflectable arms as shown in FIG. It is for making the deflection position. This engagement between the second locking member 30 of the needle sleeve 19 and the inwardly projecting boss 34 of the housing can be actuated by moving the needle sleeve 19 proximal to the housing 11. When the inwardly projecting boss 34 is not engaged with the second locking member 30, the second locking member is in the relaxed position as shown in FIG.

As shown in FIG. 6, when the second locking member 30 is in the deflection position, the first locking member 26, in particular the carrier boss 27, can move beyond the free end 37 of the deflectable arm 31. When the second locking member 30 is in the relaxed position, the head portion 29 of the first locking member cannot cross the free end 37 of the deflectable arm 31. In the relaxed position, the head portion 29 is constrained between the deflectable arms 31 of the second locking member 30 to constrain axial axial movement beyond the deflectable arm 31, or the head portion is It is stopped by the free end 37 of the deflectable arm 31 of the second locking member and constrains the axial movement in the distal direction beyond the deflectable arm 31. The movement described above is for the housing.

To assemble the device 20, the needle sleeve is inserted into the housing and the syringe 17 is inserted into the carrier 21. The carrier 21 and syringe 18 are advanced to an intermediate position within the housing 11, which is not fully inserted into the device and can be referred to as the first assembly position. The needle sleeve 19 is then moved proximally to the housing 11 and pushes the deflectable arm 31 towards the inwardly projecting boss 34 to open the second locking member 30 to the deflection position. The carrier 21 can then be further moved distally and the carrier boss 27 can cross the deflectable arm 31 when the deflectable arm 31 is opened by the inwardly projecting boss 34. This can be referred to as the second assembly position and can be the final assembly position for the carrier 21 and the syringe. However, it can be assumed that no intermediate position is required and that the carrier 21 can be fully inserted at the same time that the needle sleeve 19 is pushed down and the deflectable arm 31 is in the deflecting position. The rest of the device is then assembled, for example inserting a drive assembly into the housing to prepare the device for use. The drive assembly includes a plunger 15, a drive spring 46, and a housing end 41. The drive spring 46 is arranged to push the plunger 15 acting on the piston 14 into the syringe 18 and push the drug through the needle 17 while the injection device 10 is in use. The plunger 15 and piston 14 may be separate or single components.

During assembly, the plunger is rotated when inserted into the device either manually or by a suitable assembly tool, and the plunger boss 42 is the needle sleeve rib 47 of the needle sleeve leg 39, as can be seen in FIGS. 11 and 12. Engage with. The needle sleeve 19 is held in the retracted position while the drive assembly is inserted, and when the drive assembly is released, the needle sleeve 19 moves distally with the plunger boss 42 during device assembly and priming. Engagement with the needle sleeve rib 47 prevents the needle sleeve 19 from fully extending to the extended position. The contact between the plunger boss 42 and the needle sleeve rib 47 also hinders the downward rotation of the plunger at this position. When the needle sleeve 19 is pushed down or moved to the retracted position for injection, the plunger can rotate further, the plunger boss 42 disengages from the rib 47, and then the needle sleeve is freely in the extended position. Moving, the plunger moves freely and distally under the force of the driving spring to administer the drug.

The needle sleeve can also be held in the starting position by alternative means, for example it can be understood that the needle sleeve can engage a protrusion or retractable portion of the housing. After the injection is made, the retractable part is retracted by the actuator.

In addition, the needle sleeve can be held in the starting position by additional components such as a collar located at the distal end of the device, the needle sleeve containing a protrusion that engages the slot of the collar and when the injection is made. In addition, the collar rotates like the plunger 15 in the assembly stage, and after the injection is completed, the needle sleeve is released to reach the fully extended position. It can be appreciated that one of ordinary skill in the art can determine some alternative methods for simply capturing and releasing the two components.

When the device 20 is fully assembled, the needle sleeve 19 is released or moved distally to disengage from the inwardly projecting boss 34 to the starting position and the head portion 29 of the carrier boss 27. Stays distal to the free end 37 of the deflectable arm 31, and the needle sleeve is not fully extended by engagement with the plunger 15 described above. This arrangement here means that the device is assembled and primed for use by the user.

In order to use the device 20, the cap 12 is removed from the rest of the device, in particular the housing 11, but the device 20 may not have the cap assembly or may have already been removed. Can be understood. The cap also reduces the risk of accidental activation of the injection device, for example when the device is dropped. As can be seen in FIG. 13, when the cap 12 is on the device, the locking boss 43 of the cap 12 can engage the corresponding notch 44 of the needle sleeve 19 before the cap 12 is removed. Prevents the needle sleeve 19 from being accidentally pushed down. When the cap 12 is removed, the locking boss 43 can elastically deform into the stepped portion 45 of the housing 11 and the locking boss 43 is released from the needle sleeve notch 44. After the cap is removed, the needle is then inserted into the patient's body at the injection site to administer the drug and the needle sleeve 19 is pushed proximally from the starting position to the retracting position during the process. During this process, the needle sleeve 19 is moved proximally to the retracted position against the urging force of the urging means, eg, the spring 35. In the retracted position, the second locking portion engages the inwardly projecting boss 34, and the inwardly projecting boss is shaped to push the deflectable arm into the deflecting position. Moved, where the two deflectable arms deflect laterally with respect to the central axis of the device from the proximal end to the distal end. The spring urges the needle sleeve 19 distally toward the extension position. However, it can be understood that the urging means may be an alternative, such as bellows or compressed foam, or the sleeve can be moved to an extended position by magnetic attraction or repulsion means.

In the extended position, the first locking member is not engaged with the second locking member, the head portion 29 is on the proximal side of the deflectable arm, the second locking portion is in the relaxed position, and the spring 35 Push the needle sleeve 19 to the extended position. When the needle sleeve is in the extended position, if the needle sleeve 19 is pushed down or moved proximally after the injection, the second locking member abuts on the head portion 29 of the carrier boss 27. , Prevents axial movement of the needle sleeve 19 with respect to the carrier 21 in the proximal direction. If a proximal force is applied to the needle sleeve 19 when the needle sleeve is in the extended position, the load is dissipated through the interface between the free end of the deflectable arm 31 and the carrier boss 27. This mechanism can improve the safety of the device by effectively locking the needle sleeve 19 in an extended position surrounding the needle 17 and ensuring that the user cannot access the needle 17 after the injection is complete.

The second locking member can include only one deflectable arm located relative to the surface of the needle sleeve 19 and is cup-shaped with an alternative shaped deflectable member, eg, a corresponding T-shaped head portion 29. It can be appreciated that the deflectable member of the device, or any alternative deflectable member with a correspondingly shaped head portion 29, may be included. As mentioned above, there are several alternative deflectable or flexible members or arms that can constrain and block rigid carrier bosses.

The deflectable member and arm can be formed from a flexible material, but may also include joints, pivots, or hinges for deflection, and thus can be flexible or substantially rigid. ..

The carrier boss 27 can be flexible in that the shape of the carrier boss 27 when engaged with the second locking member 30 causes the carrier boss 27 to be constrained and stopped by a deflectable arm. I can understand.

The term "drug" or "drug" is used herein to describe one or more pharmaceutically active compounds. As described below, a drug or drug may contain at least one small molecule or macromolecule or a combination thereof in various types of formulations for the treatment of one or more diseases. Exemplary pharmaceutically active compounds include small molecules, polypeptides, peptides, and proteins (eg, hormones, growth factors, antibodies, antibody fragments, and enzymes), carbohydrates and polysaccharides, and nucleic acids, double-stranded or Included are single-stranded DNA (including naked and cDNA), RNA, antisense nucleic acids such as antisense DNA and RNA, small interfering RNA (siRNA), ribozymes, genes, and oligonucleotides. Nucleic acids can be incorporated into molecular delivery systems such as vectors, plasmids, or liposomes. Mixtures of one or more of these drugs are also contemplated.

The term "drug delivery device" includes any type of device or system in which a drug is configured to be administered to the human or animal body. Without limitation, the drug delivery device may be an injection device (eg, syringe, pen-type syringe, automatic syringe, high volume device, pump, perfusion system, or intraocular delivery, subcutaneous delivery, intramuscular delivery, or intravascular delivery. Other devices configured for delivery), skin patches (eg osmotic, chemical, microneedles), inhalers (eg nasal or lung), implants (eg coated stents, capsules) , Or a supply system for the gastrointestinal tract. The drugs described herein may be particularly useful in injection devices including needles, such as small gauge needles.

The drug or drug can be encapsulated in a primary package or "drug container" adapted for use in a drug delivery device. The drug container is, for example, a cartridge, syringe, reservoir, or other configured to provide a chamber suitable for storing one or more pharmaceutically active compounds (eg, short-term or long-term storage). Can be a vessel. For example, in some cases, the chamber can be designed to contain the drug for at least one day (eg, 1 to at least 30 days). In some cases, the chamber can be designed to store the drug for about 1 month to about 2 years. Storage can be done at room temperature (eg, about 20 ° C.) or refrigerating temperature (eg, about -4 ° C. to about 4 ° C.). In some cases, the drug container is configured to contain two or more components of the drug formulation (eg, a drug and a diluent, or two different types of drugs) individually, one in each chamber. Can be a dual chamber cartridge or can include it. In such cases, the two chambers of the dual chamber cartridge can be configured to allow mixing between two or more components of the drug or drug before and / or during dosing to the human or animal body. .. For example, the two chambers can be configured to communicate fluidly with each other (eg, via a conduit between the two chambers) and optionally allow the user to mix the two components prior to dosing. Alternatively or additionally, the two chambers can be configured to allow mixing when the ingredients are administered to the human or animal body.

The drug delivery devices and drugs described in the present invention can be used for the treatment and / or prevention of many different types of disorders. Exemplary disorders include, for example, diabetes or diabetic complications such as diabetic retinopathy, thromboembolism disorders such as deep venous thromboembolism or pulmonary thromboembolism. Further exemplary disorders are acute coronary syndrome (ACS), angina, myocardial infarction, cancer, macular degeneration, inflammation, hay fever, atherosclerosis and / or rheumatoid arthritis.

Exemplary drugs for the treatment and / or prevention of diabetes or diabetes-related complications include insulin, eg, human insulin, or human insulin analogs or derivatives, glucagon-like peptides (GLP-1), GLP-1 analogs. Alternatively, GLP-1 receptor agonists, or analogs or derivatives thereof, dipeptidyl peptidase-4 (DPP4) inhibitors, or pharmaceutically acceptable salts or admixtures thereof, or mixtures thereof can be mentioned. As used herein, the term "derivative" refers to any substance that is structurally similar enough to have substantially the same functionality or activity (eg, therapeutic effect) as the original substance. Point to.

Exemplary insulin analogs are Gly (A21), Arg (B31), Arg (B32) human insulin (insulin glargine); Lys (B3), Glu (B29) human insulin; Lys (B28), Pro (B29) human. Insulin; Asp (B28) human insulin; prolin at position B28 may be replaced with Asp, Lys, Leu, Val or Ala and Lys at position B29 may be replaced with Pro; human insulin; Ala (B26) human Insulin; Des (B28-B30) human insulin; Des (B27) human insulin and Des (B30) human insulin.

Exemplary insulin derivatives are, for example, B29-N-myristoyl-des (B30) human insulin; B29-N-palmitoyle-des (B30) human insulin; B29-N-myristoyl human insulin; B29-N-palmitoyl human insulin. B28-N-Millitoyl LysB28ProB29 Human Insulin; B28-N-Palmitoil-LysB28ProB29 Human Insulin; B30-N-Millitoyl-ThrB29LysB30 Human Insulin; B30-N-Palmitoil-ThrB29LysB30 Human Insulin; B29-N- -Glutamil) -des (B30) human insulin; B29-N- (N-lithocholyl-gamma-glutamyl) -des (B30) human insulin; B29-N- (ω-carboxyheptadecanoyl) -des (B30) human Insulin and B29-N- (ω-carboxyheptadecanoyl) human insulin. Exemplary GLP-1, GLP-1 analogs and GLP-1 receptor agonists are, for example, lixenatid / AVE0010 / ZP10 / lixemia, exenatide / exenatide-4 / byetta / vidulion / ITCA650 / AC-2993 (by the salivary gland of Hiramonster). 39 amino acid peptide produced), liraglutide / victoza, semaglutide, taspoglutide, synclia / albiglutide, duraglutide, r exenatide-4, CJC-1134-PC, PB-1023, TTP-054, langrenatide / HM-11260C, CM-3 , GLP-1 Eligen, ORMD-0901, NN-9924, NN-9926, NN-9927, Nodexen, Biador-GLP-1, CVX-096, ZYOG-1, ZYD-1, GSK-2374697, DA-3091, With MARK-701, MAR709, ZP-2929, ZP-3022, TT-401, BHM-034, MOD-6030, CAM-2036, DA-15864, ARI-2651, ARI-2255, Exenatide-XTEN and Glucagon-Xten be.

An exemplary oligonucleotide is, for example, the cholesterol-lowering antisense therapeutic agent mipomersen / kinamuro for the treatment of familial hypercholesterolemia.

Exemplary DPP4 inhibitors are bidagliptin, sitagliptin, denagliptin, saxagliptin, berberine.

Exemplary hormones include cerebral pituitary hormone or hypothalamic hormone or regulatory active peptides and their antagonists, such as gonadotropins (follitropin, leuprorelin, corion gonadotropin, menotropin), somatropine (Somatropin). ), Desmopressin, telllipresin, gonadotropin, tryptrelin, leuprorelin, buserelin, nafarerin, and gosereline.

Exemplary polysaccharides include glucosaminoglycans, hyaluronic acid, heparin, low molecular weight heparin or ultra low molecular weight heparin or derivatives thereof, or sulfated polysaccharides such as the above-mentioned polysaccharides in polysulfated form, and / or their pharmaceuticals. Examples include naturally acceptable salts. An example of a pharmaceutically acceptable salt of polysulfated low molecular weight heparin is enoxaparin sodium. Examples of hyaluronic acid derivatives are Hylan GF20 / Synbisc, sodium hyaluronate.

As used herein, the term "antibody" refers to an immunoglobulin molecule or antigen-binding portion thereof. Examples of antigen-binding moieties of immunoglobulin molecules include F (ab) and F (ab') 2 fragments that retain their ability to bind to the antigen. The antibody can be a polyclonal antibody, a monoclonal antibody, a recombinant antibody, a chimeric antibody, a deimmunized or humanized antibody, a fully human antibody, a non-human (eg, murine) antibody, or a single chain antibody. In some embodiments, the antibody has effector function and is capable of immobilizing complement. In some embodiments, the antibody has reduced or no binding ability to the Fc receptor. For example, the antibody can be an isotype or subtype, antibody fragment or mutant that does not support binding to the Fc receptor, eg, has a mutation or deletion in the Fc receptor binding region.

The term "fragment" or "antibody fragment" is a polypeptide derived from an antibody polypeptide molecule that does not contain a full-length antibody polypeptide but still contains at least a portion of a full-length antibody polypeptide capable of binding to an antigen (eg, antibody weight). Chain and / or light chain polypeptide). The antibody fragment may include a cleavage moiety of a full-length antibody polypeptide, but the term is not limited to such cleavage fragments. Antibody fragments useful in the present invention include, for example, Fab fragment, F (ab') 2 fragment, scFv (single chain Fv) fragment, linear antibody, single-specific or multi-specific antibody fragment, for example. Bispecific, trispecific, and multispecific antibodies (eg, diabody, tribody, tetrabody), minibody, chelated recombinant antibody, tribody or bibody, intrabody, nanobody, small module immunopharmaceuticals (eg, diabodies, triabodies, tetrabodies) SMIP), binding domain immunoglobulin fusion proteins, camelized antibodies, and VHH-containing antibodies. Additional examples of antigen-binding antibody fragments are known in the art.

The terms "complementarity determining regions" or "CDRs" refer to short polypeptide sequences within the variable regions of both heavy and light chain polypeptides that are primarily responsible for mediating specific antigen recognition. The term "framework regions" is used within the variable regions of both heavy and light chain polypeptides that are not CDR sequences and are primarily responsible for maintaining the proper arrangement of CDR sequences to allow antigen binding. Refers to amino acid sequences. The framework region itself is typically not directly involved in antigen binding, but as is known in the art, certain residues within the framework region of a particular antibody are directly involved in antigen binding. It can affect the ability of one or more amino acids in the CDR to interact with the antigen.

Exemplary antibodies are anti-PCSK-9 mAbs (eg, alirocumab), anti-IL-6 mAbs (eg, sarilumab), and anti-IL-4 mAbs (eg, dupilumab).

The compounds described herein can be used in pharmaceutical formulations comprising (a) a compound or a pharmaceutically acceptable salt thereof, and (b) a pharmaceutically acceptable carrier. The compound can also be used in a pharmaceutical product containing one or more other active pharmaceutical ingredients, or in a pharmaceutical product in which the compound or a pharmaceutically acceptable salt thereof is the only active ingredient. Accordingly, the pharmaceutical formulations of the present disclosure include any pharmaceutical product made by mixing the compounds described herein with a pharmaceutically acceptable carrier.

Pharmaceutically acceptable salts of any of the drugs described herein are contemplated for use in drug delivery devices. Pharmaceutically acceptable salts are, for example, acid addition salts and basic salts. The acid addition salt is, for example, an HCl or HBr salt. The basic salt is, for example, an alkali or alkaline earth metal, for example, Na + or K +, or Ca2 +, or ammonium ion N + (R1) (R2) (R3) (R4), (in the formula, R1 to R4 are each other. Independently: hydrogen, optionally substituted C1-C6-alkyl groups, optionally substituted C2-C6-alkenyl groups, optionally substituted C6-C10-aryl groups, or optionally substituted C6->. A salt having a cation selected from (meaning a C10-heteroaryl group). Further examples of pharmaceutically acceptable salts are known to those of skill in the art.

A pharmaceutically acceptable solvate is, for example, a hydrate or an alkanolate such as methanolate or ethanolate.

Those skilled in the art will appreciate that changes (additions and / or removals) of various components of the substances, formulas, devices, methods, systems, and embodiments described herein deviate from the full scope and spirit of the present disclosure. It will be appreciated that this disclosure embraces such modifications and any equivalent forms thereof.

Claims (15)

It's an injection device:
With housing;
With a carrier disposed inside the housing to hold a syringe with a needle at one end;
With a needle sleeve that is located within the housing and is axially movable between the extended and retracted positions with respect to the housing;
Includes an urging element configured to urge the needle sleeve towards an extended position;
The injection device includes a locking mechanism configured to lock the needle sleeve in the extended position after use of the injection device, the locking mechanism being:
With a first locking member provided to the carrier and protruding from the carrier;
Includes a second locking member, which is provided on the needle sleeve and includes a deflectable arm that is movable between the relaxed and deflected positions;
Here, the housing includes an inwardly projecting boss that engages with the second locking member and moves the second locking member to the deflection position when the needle sleeve is moved to the retracted position;
When the second locking member is in the deflection position, the first locking member does not engage the second locking member;
When the second locking member is in the relaxed position and the needle sleeve is in the extended position, the second locking member blocks the first locking member, thereby preventing the needle sleeve from moving back to the retracted position. device. The injection device of claim 1, wherein the needle sleeve extends further out of the housing in an extended position than in a retracted position. The deflectable arm according to claim 1 or 2, wherein the deflectable arm has a first end fixedly attached to the rest of the needle shield and a second free end away from the first end. Injection device. The needle sleeve is movable between three positions: start position, retracted position, and extended position, and the needle sleeve extends further out of the housing at the extended position than the start position and from the housing at the start position rather than the retracted position. The injection device according to any one of claims 1 to 3, further extending outward. The injection device of claim 4, wherein at the starting position, the deflectable arm is in a relaxed position and the first locking member is disposed distal to the free end of the deflectable arm. The first and second locking members are axially aligned when the second locking member is in the relaxed position, but deviate from the axial alignment when the second locking member is in the deflection position. The injection device according to any one of claims 1 to 5. The injection device of claim 3, wherein the second free end of the deflectable arm extends proximally from the first end of the deflectable arm. Any of claims 1-7, the deflectable arm is laterally deflectable with respect to the axial direction of the injection device when the second locking portion is engaged by an inwardly projecting boss of the housing. Or the injection device according to item 1. The injection device according to any one of claims 1 to 8, wherein the second locking member includes a pair of deflectable arms. The injection device according to any one of claims 2 to 9, further comprising a removable cap. The injection device according to any one of claims 1 to 10, wherein the first locking member includes a T-shaped boss protruding from a carrier. The injection device according to any one of claims 1 to 11, wherein the inwardly projecting boss of the housing is tapered toward the distal direction. The injection device according to any one of claims 1 to 12, further comprising a syringe having a needle at one end. 13. The injection device of claim 13, wherein the syringe comprises a drug. The method of assembling the injection device according to claim 1:
The process of inserting a syringe with a needle into the carrier;
A step of moving the needle sleeve proximal to the housing to the first assembly position, where the inwardly projecting boss of the housing is the second locking member of the needle sleeve at the first assembly position. Engage in and move the second locking member from the relaxed position to the deflected position, with the process;
A step of moving the carrier distally into the housing to a second assembly position, where the second locking member is in a deflection position and the first locking member is of a deflectable arm at the second assembly position. Disposed distal to the free end, the first locking member does not engage the second locking member, with the process;
In the process of releasing the needle sleeve, the urging element pushes the needle sleeve distally, the inwardly projecting boss disengages from the second locking member, and the second locking member is in the relaxed position. Movement, thereby placing the needle sleeve in the starting position, where the first locking member is located distal to the free end of the deflectable arm and the second locking member is in the relaxed position. The above-mentioned method including.

Images